In silico screening of phenolic acids and coumarins as inhibitors of avian influenza neuraminidases (N2 and N9)

Date

5-2007

Degree

Bachelor of Science in Chemistry

College

College of Arts and Sciences (CAS)

Adviser/Committee Chair

Ernesto J Del Rosario

Abstract

MUNCAL, DANILET VI ABE. College of Arts and Sciences. University of the Philippines Los Banos. May 2007. IN SILICO SCREENING OF PHENOLICS AND COUMARINS AS INHIBITORS OF AVIAN INFLUENZA NEURAMINIDASES (N2 AND N9)

Adviser: Dr. Ernesto J. del Rosario

ABSTRACT

Influenza A virus is composed of two glycoproteins namely hemagglutinin and neuraminidase. Neuraminidase which is responsible for the release of new progeny viruses. has active site that is invariant in different viral strains. Thus, it is a promising target for anti-influenza drugs.

Molecular modeling is a useful tool in drug discovery of finding and optimizing lead compounds usually by database screening. In this study, virtual screening of naturally occurring compounds (phenolics and coumarin derivatives) as neuraminidase inhibitors was conducted. Molecular modelling was done by utilizing the AUTODOCK software as well as other modeling tools such as HYPERCHEM, SPDBV and VMD. Two control dockings were conducted in order to validate the AUTODOCK protocol used as well as to validate the binding sites of the neuraminidases. The computed value for AG was -7.1 Kcal/mol and was not significantly different from the literature value -7.06 Kcal/mol. The active (binding) sites of N2 and N9 were comparable to each other and consist of: ARG156, ARG152, ARG224, ARG292. ALA246. ASP I 51, ASN294, ARG 118, GLU276, GLU277, GLU119. GLU227, ILE222. LEU134, TRP178, SER179, TYR406. All of the dockings yielded negative values for the AUTODOCK parameters, AGbinding and Edocked which signify that the reactions were spontaneous based on the second law of thermodynamics.

Commercially available anti-influenza drugs oseltamivir and zanamivir were also docked on N2 and N9. The computed values of and for phenolic acids and coumarin derivatives were comparable to those of oseltamivir and zanamivir. Other phenolic acids such as rosmarinic acid and coumarin derivatives, such as angelicide, gave more negative values for AGb,„,, and E, tea. It was also observed that oseltamivir and zanamivir preferably bind to the active sites of the enzymes. Hence, the commercially available drugs oseltamivir and zanamivir as well as phenolic acids and coumarin derivatives, were found to be competitive inhibitors of neuraminidases N2 and N9. The most promising potential neuraminidase inhibitor was rosmarinic acid among the phenolic acids screened and angelicide among the coumarin derivatives.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

LG 993.5 2007 C4 M86

Document Type

Thesis

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